Dengue virus is a serious endemic disease that infects nearly 400 million people annually. This disease can cause dengue fever, dengue hemorrhagic fever, and dengue shock syndrome which are all characterized by headaches, nausea, vomiting, weakness, break-bone fever, severe muscle and joint pain, and in extreme cases, vascular leakage (leaking of the veins).
Dengue virus is considered the leading cause of death and illness in the tropical regions of the world, such as Southeast Asia, Latin America, and the Pacific Islands. The World Health Organization (WHO) states that the global incidence of dengue has increased dramatically in recent decades and about half of the world' s population is now at risk. Dengue virus is transmitted through mosquito bites and has four different strains, each capable of causing the full spectrum of the disease.
Currently, there is no approved medicine or vaccine against dengue virus, but scientists and drug companies alike are researching this virus continuously in order to find a cure. Recently, one vaccine candidate, called CYD-TDV vaccine, has emerged as the most promising solution to this globally endemic disease.
Figure 1. A TEM micrograph showing dengue virus virions (the cluster of dark dots near the center). Taken from: https://en.wikipedia.org/wiki/Dengue_virus
References:
1. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/genomes/VirusVariation/dengue_help.html (accessed on Feb 2, 2017).
2. Center for Disease Control and Prevention. https://www.cdc.gov/dengue/index.html (accessed on Feb 2, 2017)
3. Guy, B.; Jackson, N., Dengue vaccine: hypotheses to understand CYD-TDV-induced protection. Nature Reviews Microbiology2015, 14, (1), 45-54.
4. Rothman, A. L., Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nature Reviews Immunology2011, 11, (8), 532-543
5. Guy, B.; Barrere, B.; Malinowski, C.; Saville, M.; Teyssou, R.; Lang, J., From research to phase III: Preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine. Vaccine 2011, 29, (42), 7229-7241.
Dengue virus's genome codes for seven non-structural proteins and three structural ones. The structural proteins are the envelope (E), capsid (C), and precursor membrane (prM) proteins. The target of interest is the envelope protein (E) since it contains all the virus's antigenic markers and binding sites. In addition, the E glycoprotein is one of the main components of the virus's surface and displays the highest affinity to antibodies, making it a favorable target for vaccine development.
Figure 2: The several residues that make up the different parts of the E glycoprotein (a). This protein's structural shape (b) and location on dengue virus (c) are shown as well. The E protein has 3 domains (domains I, II, and III) which are colored red, yellow, and blue respectively. Taken from: http://www.nature.com.ezproxy.lib.utexas.edu/nature/journal/v427/n6972/fig_tab/nature02165_F1.html
Size: Usually 70-80 Å long and 30-50 Å wide.
Molecular Weight: About 53 kDa
Location: E glycoprotein is found all around the surface of the virus.
Function in a normal cell: Since envelope proteins contain the binding sites and antigenic markers of the dengue virus, they play a key role in the virus's life cycle by allowing the virus to identify and enter its host cells.
Drug Information:
Chimera yellow disease -tetravalent dengue virus (CYD-TDV) vaccine holds promise as the world's first vaccine against dengue virus. The vaccine's serum contains four, live-attenuated, chimeric dengue vaccines on a yellow fever 17D backbone (YF 17D), with each chimera expressing the envelope (E) and precursor membrane (prM) genes of one of the four dengue virus serotypes. Broadly neutralizing human antibodies will bind to the E and prM proteins of the attenuated viruses causing the body to immunize itself against all four existing strains of the dengue virus. It is vital that the individual be immunized against all four strains simultaneously since developing an immunity against only one serotype will not protect the person from the remaining three, which can all lead to the same devastating illnesses to be formed.
No chemical drug is currently being sternly researched in order to decrease dengue's potency; however, acetaminophen has been prescribed in various cases to help treat dengue fever and relieve some symptoms, but it does not extinguish the fever or decrease the mortality rate of dengue fever.
Schematic figure of vaccine:
Crystal structure of dengue 2 virus envelope glycoprotein in complex with the Fab fragment of the broadly neutralizing human antibody EDE2 B7. Taken from: http://www.rcsb.org/pdb/explore/explore.do?structureId=4UT6
Serial number: 86633354
Registration number: 4877362
CVX code of dengue fever: 56
Delivery method: Injection by needle. A three dose regimen is used for this vaccination in which a vaccine is injected once at 0, 6 and 12 months.
Side effects: There are no recorded side effects associated with Dengvaxia® ,and long-term safety has been fairly established.
Other names: Dengvaxia®
Maker or company: Sanofi Pasteur is currently synthesizing Dengvaxia®.
Is it patented? Yes, Sanofi Pasteur has patented this vaccine. Patent Number: US20080085288A1.
Clinical Trials Info: Dengvaxia is currently in Phase III clinical trials and is being conducted on children aged 9 to 16 years in Latin America and 2 to 14 years in Asia. Some trials are still ongoing or recruiting and others have been completed.
Origin: The development of a vaccine for dengue fever began as early as 1929, but has been hindered by incomplete knowledge of the virus's pathogenesis. Nowadays, with a more complete understanding of dengue virus, a vaccine is being developed to immunize people against this virus and end its potency.
Alternatives to this vaccine: Other vaccine candidates are being researched as well, such as inactivated whole viruses, recombinant subunit proteins, and DNA and viral vectored vaccines.
Miscellaneous: Acetaminophen has been prescribed to alleviate some symptoms of dengue fever, but it does not terminate the fever. Its formula is C8H9NO, its CAS number is 103-90-2, its molecular weight is 151.16 g/mol, and it is produced under different brand names, such as Tylenol, Panadol, Anacin, and Mapap.
Figure 4. The chemical structure of acetaminophen. Taken from: https://scifinder-cas-org.ezproxy.lib.utexas.edu/scifinder/view/scifinder/scifinderExplore.jsf
Other uses: CYD-TDV vaccine is being synthesized solely to immunize the body against dengue virus. On the other hand, acetaminophen is an analgesic that can treat minor aches and pains in general, and reduce fever.
Disease/Drug of interest:
Motivation and Background:
Dengue virus is a serious endemic disease that infects nearly 400 million people annually. This disease can cause dengue fever, dengue hemorrhagic fever, and dengue shock syndrome which are all characterized by headaches, nausea, vomiting, weakness, break-bone fever, severe muscle and joint pain, and in extreme cases, vascular leakage (leaking of the veins).
Dengue virus is considered the leading cause of death and illness in the tropical regions of the world, such as Southeast Asia, Latin America, and the Pacific Islands. The World Health Organization (WHO) states that the global incidence of dengue has increased dramatically in recent decades and about half of the world' s population is now at risk. Dengue virus is transmitted through mosquito bites and has four different strains, each capable of causing the full spectrum of the disease.
Currently, there is no approved medicine or vaccine against dengue virus, but scientists and drug companies alike are researching this virus continuously in order to find a cure. Recently, one vaccine candidate, called CYD-TDV vaccine, has emerged as the most promising solution to this globally endemic disease.
References:
1. National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/genomes/VirusVariation/dengue_help.html (accessed on Feb 2, 2017).
2. Center for Disease Control and Prevention. https://www.cdc.gov/dengue/index.html (accessed on Feb 2, 2017)
3. Guy, B.; Jackson, N., Dengue vaccine: hypotheses to understand CYD-TDV-induced protection. Nature Reviews Microbiology 2015, 14, (1), 45-54.
4. Rothman, A. L., Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nature Reviews Immunology 2011, 11, (8), 532-543
5. Guy, B.; Barrere, B.; Malinowski, C.; Saville, M.; Teyssou, R.; Lang, J., From research to phase III: Preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine. Vaccine 2011, 29, (42), 7229-7241.
External links:
1. World Health Organization. http://www.who.int/mediacentre/factsheets/fs117/en/2. Nature. http://www.nature.com/scitable/topicpage/dengue-viruses-22400925
3. Dengue Virus Envelope Proteins. https://microbewiki.kenyon.edu/index.php/Dengue_virus_envelope_proteins
4. Medscape, Dengue Treatment and Management.
http://emedicine.medscape.com/article/215840-treatment?pa=oQ9pWhOIlgwWZokAsQ3wUYXkXe8Br7HXwj5g0Uo4eQOgynXGq38Oy%2B2yLi0JePVUBHdXlnV203Bw2cQGra411A8oyMK1o%2FrQdMeQkhfWxCQ%3D
Target Information:
Dengue virus's genome codes for seven non-structural proteins and three structural ones. The structural proteins are the envelope (E), capsid (C), and precursor membrane (prM) proteins. The target of interest is the envelope protein (E) since it contains all the virus's antigenic markers and binding sites. In addition, the E glycoprotein is one of the main components of the virus's surface and displays the highest affinity to antibodies, making it a favorable target for vaccine development.
Size: Usually 70-80 Å long and 30-50 Å wide.
Molecular Weight: About 53 kDa
Location: E glycoprotein is found all around the surface of the virus.
Function in a normal cell: Since envelope proteins contain the binding sites and antigenic markers of the dengue virus, they play a key role in the virus's life cycle by allowing the virus to identify and enter its host cells.
Drug Information:
Chimera yellow disease -tetravalent dengue virus (CYD-TDV) vaccine holds promise as the world's first vaccine against dengue virus. The vaccine's serum contains four, live-attenuated, chimeric dengue vaccines on a yellow fever 17D backbone (YF 17D), with each chimera expressing the envelope (E) and precursor membrane (prM) genes of one of the four dengue virus serotypes. Broadly neutralizing human antibodies will bind to the E and prM proteins of the attenuated viruses causing the body to immunize itself against all four existing strains of the dengue virus. It is vital that the individual be immunized against all four strains simultaneously since developing an immunity against only one serotype will not protect the person from the remaining three, which can all lead to the same devastating illnesses to be formed.
No chemical drug is currently being sternly researched in order to decrease dengue's potency; however, acetaminophen has been prescribed in various cases to help treat dengue fever and relieve some symptoms, but it does not extinguish the fever or decrease the mortality rate of dengue fever.
Schematic figure of vaccine:
Serial number: 86633354
Registration number: 4877362
CVX code of dengue fever: 56
Delivery method: Injection by needle. A three dose regimen is used for this vaccination in which a vaccine is injected once at 0, 6 and 12 months.
Side effects: There are no recorded side effects associated with Dengvaxia® ,and long-term safety has been fairly established.
Other names: Dengvaxia®
Maker or company: Sanofi Pasteur is currently synthesizing Dengvaxia®.
Is it patented? Yes, Sanofi Pasteur has patented this vaccine. Patent Number: US20080085288A1.
Clinical Trials Info: Dengvaxia is currently in Phase III clinical trials and is being conducted on children aged 9 to 16 years in Latin America and 2 to 14 years in Asia. Some trials are still ongoing or recruiting and others have been completed.
Origin: The development of a vaccine for dengue fever began as early as 1929, but has been hindered by incomplete knowledge of the virus's pathogenesis. Nowadays, with a more complete understanding of dengue virus, a vaccine is being developed to immunize people against this virus and end its potency.
Alternatives to this vaccine: Other vaccine candidates are being researched as well, such as inactivated whole viruses, recombinant subunit proteins, and DNA and viral vectored vaccines.
Miscellaneous: Acetaminophen has been prescribed to alleviate some symptoms of dengue fever, but it does not terminate the fever. Its formula is C8H9NO, its CAS number is 103-90-2, its molecular weight is 151.16 g/mol, and it is produced under different brand names, such as Tylenol, Panadol, Anacin, and Mapap.
CYD-TDV vaccine is being synthesized solely to immunize the body against dengue virus. On the other hand, acetaminophen is an analgesic that can treat minor aches and pains in general, and reduce fever.